This proposal is concerned with the interactions between neurons and their target cells that govern synapse formation and maintenance. Frog nerve-muscle preparations are used, and we are now mainly addressing the question of what factor(s) regulate the number, location, size and efficacy of neuromuscular synapses, normally and following regeneration. In particular, our work is focused upon the following problems: (a) We have shown that two or more axon terminals from two foreign nerves, ending on a given skeletal muscle fiber, compete with one another, one tending to become dominant, the other reduced in its effectiveness. This being the case, we wish to elucidate the mechanisms of interaction, how the effect is mediated, and what morphological correlates of it can be found. As a corollary of this problem, we are interested in determining whether there is comparable competitive interaction between the endings in normally innervated muscle, i.e., between the axons of one nerve. (b) When synapses appear to vary widely in efficacy, is this always correlated with synaptic size, or can other factors modulate synaptic effectiveness? (c) How does the strength of a given synapse depend on the number of terminals being maintained by the motoneuron in question? (d) What governs where a regenerating nerve will form a synapse, and the time course of development of pre- and post-synaptic specializations during synapse regeneration?